Lack of evidence for infection with known human and animal retroviruses in patients with chronic fatigue syndrome

Abstract:

We investigated 21 patients with chronic fatigue syndrome who were identified through the surveillance system of the Centers for Disease Control and Prevention (CDC) in Atlanta for the presence of several human and animal retroviruses. In addition, we evaluated 21 CDC employee controls matched with the patients for age (+/- 5 years), gender, and race.

The viruses tested included human T-lymphotropic viruses types I and II; human spuma retrovirus; simian T-lymphotropic virus type I; simian retroviruses types 1, 2, and 3; bovine leukemia virus; feline leukemia virus; and gibbon ape leukemia virus.

Samples of peripheral blood lymphocytes and leukocytes from patients and controls were analyzed in a blinded fashion for retroviral sequences; polymerase chain reaction (PCR) amplification assays and Southern blot hybridization to 32P-labeled internal oligoprobes were used. All PCR assays were optimized for maximal sensitivity on respective infected cell lines or plasmids, and sensitivity controls were included in each experiment.

All samples from patients and controls were negative for the tested retroviral sequences. Our data indicate that none of these retroviruses plays an etiologic role or is a cofactor in the chronic fatigue syndrome illnesses of our study population.

 

Source: Heneine W, Woods TC, Sinha SD, Khan AS, Chapman LE, Schonberger LB, Folks TM. Lack of evidence for infection with known human and animal retroviruses in patients with chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S121-5. http://www.ncbi.nlm.nih.gov/pubmed/8148438

 

Inability of retroviral tests to identify persons with chronic fatigue syndrome, 1992

Abstract:

Chronic fatigue syndrome (CFS) is characterized by prolonged, debilitating fatigue. Although the cause of CFS unknown, CDC and researchers in other organizations have been investigating whether infection with a previously unidentified retrovirus might be an etiologic factor. Based on reports suggesting that retroviral infection with a human T-lymphotropic virus type 2 (HTLV-II)-like retrovirus or a spumavirus might be associated with CFS, some research and commercial laboratories developed assays to test specimens from persons with CFS. Even though the hypothesized association between infection with retroviruses and CFS has not been confirmed, these tests are used commonly to evaluate patients with CFS. This report summarizes the findings of a controlled, blinded study conducted in 1992 to determine whether three retroviral tests can distinguish serologically between patients with CFS (i.e., case-patients) and healthy controls.

 

Source: Centers for Disease Control and Prevention (CDC). Inability of retroviral tests to identify persons with chronic fatigue syndrome, 1992. MMWR Morb Mortal Wkly Rep. 1993 Mar 19;42(10):183, 189-90. http://www.ncbi.nlm.nih.gov/pubmed/8446093

 

Assessment of a retrovirus sequence and other possible risk factors for the chronic fatigue syndrome in adults

Abstract:

OBJECTIVE: To assess whether the human T-lymphotropic virus type II (HTLV-II) gag gene sequence, a purportedly new laboratory marker of the chronic fatigue syndrome (CFS), and other possible risk factors for CFS, particularly those associated with retroviral transmission, are associated with well-characterized CFS.

DESIGN: Two matched case-control studies.

SETTING: The metropolitan Atlanta area.

PATIENTS: Twenty-one patients with CFS who were identified by the Centers for Disease Control and Prevention CFS surveillance system; 21 CDC employee controls (laboratory study) and 42 neighborhood controls (risk-factor study) who were matched to patients by age, race, and gender.

MEASUREMENTS: Peripheral blood lymphocytes and leukocytes were assayed for the HTLV-II gag gene sequence by polymerase chain reaction and specific Southern blot hybridization. Questionnaires elicited demographic and clinical information and a history of exposures associated with retrovirus transmission (for example, blood transfusions, sexual practices, intravenous drug use).

RESULTS: All patients were white and 86% were female. The median age at illness onset was 34 years (range, 16 to 51 years). The HTLV-II gag gene sequence was not identified in the blood of any patient or control under conditions in which the appropriate assay controls were positive. No statistical differences were observed between patients and controls in frequency of blood transfusions (10% compared with 7%), median number of sex partners before illness (3 compared with 3), bisexual or homosexual behavior (14% compared with 7%), intravenous drug use (0% compared with 0%), and other factors associated with retroviral infection.

CONCLUSIONS: The HTLV-II gag gene sequence was not a marker for CFS in this small study of well-defined patients, nor did other characteristics of the patients and controls support the hypothesis that a retrovirus, transmitted by usual modes, was a cause of CFS.

 

Source: Khan AS, Heneine WM, Chapman LE, Gary HE Jr, Woods TC, Folks TM, Schonberger LB. Assessment of a retrovirus sequence and other possible risk factors for the chronic fatigue syndrome in adults. Ann Intern Med. 1993 Feb 15;118(4):241-5. http://www.ncbi.nlm.nih.gov/pubmed/8420441

 

Japanese patients with chronic fatigue syndrome are negative for known retrovirus infections

Abstract:

Although chronic fatigue syndrome (CFS) is known to be the syndrome that begins with an acute flu-like illness that may be due to the exposure to an infectious agent, there has been no convincing evidence on the causative agents.

Recently, human T-lymphotropic virus type II (HTLV-II)-like virus has been reported to be associated with the CFS by using HTLV Western blot analysis and polymerase chain reaction. However, some investigators could not detect HTLV-II by indirect immunofluorescence analysis.

Lately, CFS patients have been reported in Japan. We detected all 30 tested patients with CFS were seronegative for HTLV-II, HTLV-I and HIV by specific peptide ELISA and Western blot. Further, PCR analysis was negative for HTLV-II and retrovirus was not detected by coculture method with patients’ PBMC. Thus, known human retrovirus infections do not cause a CFS in Japan.

 

Source: Honda M, Kitamura K, Nakasone T, Fukushima Y, Matsuda S, Nishioka K, Matsuda J, Hashimoto N, Yamazaki S. Japanese patients with chronic fatigue syndrome are negative for known retrovirus infections. Microbiol Immunol. 1993;37(10):779-84. http://www.ncbi.nlm.nih.gov/pubmed/7507200

 

Search for retrovirus in the chronic fatigue syndrome

Abstract:

AIM: To examine peripheral blood and skeletal muscle from patients with chronic fatigue syndrome for exogenous retrovirus.

METHODS: Blood samples from 30 patients and muscle biopsy specimens of 15 patients were examined for retroviral sequences by DNA extraction, polymerase chain reaction (PCR), and Southern blotting hybridisation. Sera were examined for human foamy virus by western immunoblotting and indirect immunofluorescence techniques.

RESULTS: No differences between the patient and control populations was found for any of the PCR primer sets used (gag, pol, env, and tax regions of HTLV I/II). An endogenous gag band was observed in both the patient and control groups. All sera were negative for antibody to human foamy virus.

CONCLUSION: The results indicate that there is no evidence of retroviral involvement in the chronic fatigue syndrome.

 

Source: Gow JW, Simpson K, Schliephake A, Behan WM, Morrison LJ, Cavanagh H, Rethwilm A, Behan PO. Search for retrovirus in the chronic fatigue syndrome. J Clin Pathol. 1992 Dec;45(12):1058-61. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC494996/ (Full article)

 

Chronic fatigue syndrome and virus infection: human herpesvirus 6 (HHV-6) infection

Abstract:

Chronic fatigue syndrome (CFS) is newly-recognized disease characterized by chronic and debilitating fatigue. It has been suggested that viral infection may be involved in this syndrome from the results of clinical examination, including increased activity of 2′,5′-synthetase in leukocytes of patients. The following viruses have been reported as etiologic agents of this disease. First, many studies have found elevated levels of IgG to viral capsid antigen and early antigens to Epstein-Barr virus (EBV), but low titer or absence of antibody to EBV-associated nuclear antigen. Second, the enteroviruses have also been implicated as possible causative agent of CFS, because virus could be isolated from patients. Recently it was also reported that antibodies to human T-lymphotropic virus (HTLV) and HTLV type II (HTLV-II) gag sequence were detectable in patients. Finally several reports state that human herpesvirus 6 (HHV-6) could be isolated from CFS patients in the high frequency. In conclusion, it is still early to identify the etiologic agent from these reports, and more effort is needed.

 

Source: Yamanishi K. [Chronic fatigue syndrome and virus infection: human herpesvirus 6 (HHV-6) infection]. Nihon Rinsho. 1992 Nov;50(11):2612-6. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1337558

 

Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome

Abstract:

Chronic fatigue immune dysfunction syndrome (CFIDS) is a recently recognized illness characterized by debilitating fatigue as well as immunological and neurological abnormalities [Straus, S.E. (1988) J. Inf. Dis. 157, 405-412]. Once thought to be caused by Epstein-Barr virus, it is now thought to have a different but unknown etiology.

We evaluated 30 adult and pediatric CFIDS patients from six eastern states for the presence of human T-lymphotropic virus (HTLV) types I and II by Western immunoblotting, polymearse chain reaction, and in situ hybridization of blood samples.

The majority of patients were positive for HTLV antibodies by Western blotting and for HTLV-II gag sequences by polymerase chain reaction and in situ hybridization. Twenty nonexposure healthy controls were negative in all assays. These data support an association between an HTLV-II-like virus and CFIDS.

 

Source: DeFreitas E, Hilliard B, Cheney PR, Bell DS, Kiggundu E, Sankey D, Wroblewska Z, Palladino M, Woodward JP, Koprowski H. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2922-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC51352/ (Full article)